Atherosclerosis is this nation's leading cause of death for males and females, and blacks and whites. There is mounting evidence that the oxidation of blood low density lipoproteins (LDL) plays and important -role in the pathogenesis of this disease. LDL oxidation can be prevented by several dietary antioxidants, in particular, vitamin C, vitamin E, and beta-carotene. There is preliminary evidence that dietary antioxidants may slow the natural history of atherosclerosis in humans. Until now studies in this area have included predominantly white males with symptomatic disease. We propose to examine the role of dietary antioxidants in the etiology of atherosclerosis in both sexes and in whites and blacks. Specifically, we will test the following hypothesis: Individuals in the lowest quintile of vitamin C, vitamin E and carotenoid consumption are at higher risk of asymptomatic atherosclerosis than those consuming greater amounts. We will study the relationship using data from the Atherosclerosis Risk in Communities (ARIC) Study, an on-going study of atherosclerosis in four U.S. communities. Roughly 15,800 men and women aged 45-64 years participated. The study population represents communities from areas with high and low atheroclerotic heart disease mortality: urban, suburban and rural settings; men, women, blacks and whites. Antioxidant intake was assessed by a validated food frequency questionnaire and a diet supplement survey. We will test the hypothesis in a case-control analysis. Cases will be those with asymptomatic carotid artery atherosclerosis as determined by B-mode ultrasonography. Controls will be those without evidence of carotid artery atherosclerosis. Secondary analyses will determine which sex-race subgroups may be at particular risk due to low antioxidant consumption. If the protective relationships between vitamin C, vitamin E and/or carotenoid intake and atherosclerosis are confirmed there would be both short-term and long-term benefit. In the short-term, a confirmation will provide additional support for the antioxidant-atherosclerosis hypothesis and would indicate in which population sub-groups further study might be particularly fruitful. In the long-term, it may eventually lead to a new prevention strategy, the increased consumption of antioxidant rich foods. Given the public health burden from atherosclerosis in the United States additional opportunities for prevention are very much needed.